8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect (ITCO#2)

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Endocrine-Related                        L Lamartina, G Grani et al.            TNM staging of DTC                            25:3            L7–L11
 Cancer

RESEARCH LETTER

8th edition of the AJCC/TNM staging system of
thyroid cancer: what to expect (ITCO#2)

Dear Editor,
Differentiated thyroid cancer (DTC) has become one of                            cancer since 2013 (Lamartina et al. 2017). Cases included
the most frequently diagnosed malignancies, especially                           in our study met all the following criteria: (1) histological
among women and young adults (Davies & Welch 2014).                              diagnosis of thyroid cancer of follicular origin; (2) date
The outcomes are generally very good: disease recurrence                         of diagnosis between 1 January 2013 and 1 March 2017;
rates are low (Durante et al. 2013), and survival rates are                      (3) complete data on primary tumor pathology, including
excellent (Tuttle et al. 2017a). Evidence-based management                       minimal ETE, and initial treatment.
is crucial to avoid overtreatment of these low-risk tumors,                           The selected cohort analyzed included 1765 patients,
which can reduce quality of life and yet identify accurately                     76% of whom were females. The median age at diagnosis
those requiring more aggressive therapy. Several staging                         was 48 years (range: 10–87). Total thyroidectomy
systems have been generated to inform DTC management.                            (or    lobectomy + completion      thyroidectomy)        was
One of the most widely used is the tumor-node-metastasis                         performed in 1727 (98%) cases and followed by radioiodine
(TNM) classification elaborated by the American Joint                            remnant ablation in 954 (55%). Neck dissection was
Committee on Cancer (AJCC), which allows to predict the                          performed in 711 (40%) of the 1765 patients. Most of the
risk of cancer-related death. The 8th edition of the AJCC                        tumors (n = 1657, 94%) were papillary thyroid cancers;
staging system for thyroid cancer (AJCC-8) was recently                          the remaining 108 (6%) were follicular or Hürthle cell
published (Tuttle et al. 2017b) and is scheduled to be                           carcinomas. Estimated risks of recurrence calculated
implemented on 1 January 2018. Revision of the system                            according to the criteria recommended in 2015 by the
was undertaken to address several specific limitations                           American Thyroid Association were low in 1046 (59%),
identified in the 7th edition (AJCC-7), which has been in                        intermediate in 612 (35%) and high in 107 (6%) of the
use since 2009 (Tuttle et al. 2017a,b). The main changes                         cases. Microscopic ETE was found in 410 (23%), but only
(described in detail below and summarized in Table 1)                            40 (2%) of these patients had gross invasion of the strap
are as follows: (1) an increase in the age threshold for                         muscles (sternohyoid, sternothyroid, thyroidhyoid and/or
defining high risk of thyroid cancer-related death and                           omohyoid muscles). Lymph node status for the 711
(2) a decrease in the unfavorable prognostic significance                        patients who underwent lymph node dissection was as
attributed to certain findings (i.e., cervical lymph node                        follows: pN0 (no metastasis) in 338 (19%); pN1a (central
metastases and microscopic extrathyroidal extension                              compartment metastases) in 221 (12%) and pN1b (lateral
(ETE), which has been re-defined to include only invasion                        compartment metastases) 152 (9%). Distant metastases
of the perithyroidal muscle).                                                    were found in 32 (1.8%) patients.
     To assess the impact of transitioning to the new AJCC-8                          As noted above, in the AJCC-8, the age threshold for
in terms of stage distribution and prevalence of each stage                      high risk of disease-specific mortality was raised from
class, we analyzed data extracted from the web-based                             45 years – the median age at diagnosis in several published
database of the Italian Thyroid Cancer Observatory (ITCO)                        series – to 55 years (Nixon et al. 2016). This change
(www.itcofoundation.org), a network of thyroid cancer                            increases the proportion of relatively young patients
centers (including primary and tertiary centers) located                         whose mortality risk can be defined solely on the basis
throughout Italy. The database includes prospectively                            of the absence or presence of distant metastases (stages
updated, observational data provided by ITCO member                              I and II, respectively) (Table 1). As shown in Fig. 1A,
centers on patients consecutively diagnosed with thyroid                         the percentage of patients classified as ‘younger’ in our

 http://erc.endocrinology-journals.org     © 2018 Society for Endocrinology
 https://doi.org/10.1530/ERC-17-0453          Published by Bioscientifica Ltd.
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Endocrine-Related                            L Lamartina, G Grani et al.              TNM staging of DTC                            25:3                   L8
     Cancer

Table 1 AJCC TNM staging: 7th and 8th editions.

7th                                                                                      8th
edition          Age
Endocrine-Related                        L Lamartina, G Grani et al.            TNM staging of DTC                              25:3                   L9
 Cancer

                                                                                                     Figure 1
                                                                                                     DTC stage distributions in the ITCO cohort based
                                                                                                     on the 7th and 8th editions of the AJCC system.
                                                                                                     (A) The younger subcohorts defined by the
                                                                                                     AJCC-7 and AJCC-8 comprised 698 patients aged
                                                                                                     55 years, respectively. Restaging with
                                                                                                     the AJCC-8 increased the percentages of patients
                                                                                                     with stage I (from 56 to 64%) or II (from 8 to
                                                                                                     31%) disease.

to stage III (Tuttle et al. 2017b), or regional metastases plus                  a far better agreement was found for the presence of gross
microscopic ETE (18/193, 9%). It should be noted that,                           ETE with invasion of perithyroidal muscles compared
differently from the AJCC-7, the ITCO database has always                        with invasion of perithyroidal fat only. The extensive
classified level VII lymph node metastases as central neck                       downstaging effect of the AJCC-8 was intentional: the
node lesions. This reflects the well-known difficulties in                       TNM staging system assesses the risk of DTC-related
distinguishing levels VI and VII and is consistent with                          death, which has proved to be very low for most patients.
the revised definitions adopted in the AJCC-8 (Tuttle                            Indeed, the results of retrospective cohort analyses
et al. 2017b). Since the same classification was also used                       confirm that the AJCC-8 provides more accurate estimates
for our AJCC-7 staging, some cases that met the criteria                         of DTC patients’ DSS (Kim et al. 2017a,b, Pontius et al.
for AJCC-7 stage IVa may have been erroneously reported                          2017, Tuttle et al. 2017a). From a practical standpoint,
herein as stage III. As for the entire cohort, application                       application of the AJCC-8 criteria can be expected to
of the AJCC-8 criteria downstaged 477 (27%) of the 1765                          simplify the staging process for most DTC patients, who
DTC patients. As a result, the estimated risk for 10-year                        will now be classified as ‘younger’. It will also markedly
disease-specific mortality was 40%) were restricted to                       risk (those with stages III–IV disease, where the DSS-10
2% (31/1765) of the patients who were 55 or older and                            is
Endocrine-Related                        L Lamartina, G Grani et al.            TNM staging of DTC                                  25:3                 L10
 Cancer

                                              Graziano Ceresini13                             16Dipartimento di Medicina Clinica e Sperimentale,
                                                   Rocco Bruno14                                           Università di Catania, Catania, Italy
                                                  Ruth Rossetto15                17Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche,

                                              Salvatore Tumino16                                    Università di Roma Sapienza, Latina, Italia
                                                Marco Centanni17                         18Unità Operativa Semplice Dipartimentale, Ospedale

                                          Domenico Meringolo18                                         Bentivoglio, Ausl Bologna, Bologna, Italy
                                          Maria Grazia Castagna19                               19Dipartimento di Scienze Mediche, Chirurgiche

                                           Domenico Salvatore20                                 e Neurologiche, Università di Siena, Siena, Italy
                                             Antonio Nicolucci21                    20Dipartimento di Medicina Clinica e Chirurgia, Università

                                             Giuseppe Lucisano21                                 degli Studi di Napoli ‘Federico II’, Napoli, Italy
                                                Sebastiano Filetti1                 21Center for Outcomes Research and Clinical Epidemiology,

                                                Cosimo Durante1                                                                      Pescara, Italy

       1Dipartimento    di Medicina Interna e Specialità Mediche,                         (Correspondence should be addressed to S Filetti:
                       Università di Roma Sapienza, Roma, Italy                                            sebastiano.filetti@uniroma1.it)
        2Dipartimento di Scienze Mediche, Università di Torino,                      *(L Lamartina and G Grani contributed equally to this
                                                     Torino, Italy                                                                  work)
  3Unità Operativa di Endocrinologia e Malattie del Ricambio,

   Azienda Ospedaliera Universitaria di Ferrara, Ferrara, Italy
              4Dipartimento di Medicina, Università di Perugia,                  Declaration of interest
                                                                                 The authors declare that there is no conflict of interest that could be
                                                    Perugia, Italy
                                                                                 perceived as prejudicing the impartiality of this article.
    5Dipartimento di Scienze Mediche, Ospedale Casa Sollievo

           della Sofferenza-IRCCS, San Giovanni Rotondo, Italy
     6Cattedra di Chirurgia Endocrina, Area di Endocrinologia
                                                                                 Funding
  e Malattie Metaboliche, Fondazione Policlinico Universitario                   This paper was funded by the Umberto Di Mario Foundation.
         Agostino Gemelli, Università Cattolica del Sacro Cuore,
                                                      Roma, Italy
            7Cattedra di Endocrinologia, Area di Endocrinologia
                                                                                 Author contribution statement
  e Malattie Metaboliche, Fondazione Policlinico Universitario                   Livia Lamartina and Giorgio Grani: data management and interpretation,
                                                                                 analysis and writing. Antonio Nicolucci and Giuseppe Lucisano: statistical
         Agostino Gemelli, Università Cattolica del Sacro Cuore,
                                                                                 analysis and data interpretation. Emanuela Arvat, Alice Nervo, Maria
                                                      Roma, Italy                Chiara Zatelli, Roberta Rossi, Efisio Puxeddu, Silvia Morelli, Massimo
   8Unità di Medicina Nucleare, Università di Roma Sapienza,                     Torlontano, Michela Massa, Rocco Bellantone, Alfredo Pontecorvi,
                                                                                 Teresa Montesano, Loredana Pagano, Lorenzo Daniele, Laura Fugazzola,
                                                      Roma, Italy
                                                                                 Graziano Ceresini, Rocco Bruno, Ruth Rossetto, Salvatore Tumino, Marco
            9Unità di Endocrinologia, Dipartimento di Medicina
                                                                                 Centanni, Domenico Meringolo, Maria Grazia Castagna and Domenico
               Traslazionale, Università del Piemonte Orientale,                 Salvatore: data collection and analysis, and manuscript editing. Cosimo
                                                                                 Durante and Sebastiano Filetti: concept, data interpretation, analysis and
                                                    Novara, Italy
                                                                                 manuscript editing.
       10Unità di Patologia, Ospedale Mauriziano Umberto I di

                                             Torino, Torino, Italy
       11Divisione di Malattie Endocrine e Metaboliche, Istituto
                                                                                 Acknowledgements
                        Auxologico Italiano IRCCS, Milano, Italy                 G G and L L contributed to this paper as recipients of the PhD program of
      12Dipartimento di Fisiopatologia Medico-Chirurgica e dei                   Biotechnologies and Clinical Medicine of the University of Rome, Sapienza.
      Trapianti, Università degli Studi di Milano, Milano, Italy                 Medical editing services were provided by M E Kent and funded by the
                                                                                 Umberto Di Mario Foundation. The authors thank all the members of the
13Dipartimento di Medicina e Chirurgia, Università di Parma,
                                                                                 ITCO foundation: Ancona: Alessia Smerilli, Augusto Taccaliti. Bari: Vincenzo
                                                     Parma, Italy                Triggiani, Giuseppina Renzulli. Brescia: Maria Beatrice Panarotto. Catania:
          14Unità di Endocrinologia, Ospedale di Tinchi-Pisticci,                Simona Quartararo, Dario Tumino. Ferrara: Ettore Degli Uberti. La Spezia:
                                                                                 Laura Camerieri, Mario Cappagli. Latina: Maria Giulia Santaguida.
                                                    Matera, Italy                Livorno: Daniele Barbaro, Paola Lapi. Matera: Antonella Carbone. Milano:
   15Divisione di Endocrinologia, Diabetologia e Metabolismo,                    Università degli Studi di Milano: Carla Colombo, Simone De Leo, Luca
Dipartimento di Scienze Mediche, Ospedale Molinette, A.O.U.                      Persani; Univesrità Humanitas di Milano: Andrea Lania. Napoli: Università
                                                                                 degli Studi di Napoli ‘Federico II’: Tommaso Porcelli. Istituto Nazionale
      Città della Salute e della Scienza di Torino, Università di                Tumori ITCCS ‘Fondazione G. Pascale’: Maria Grazia Chiofalo, Luciano
                                             Torino, Torino, Italy               Pezzullo. Novara: Gianluca Aimaretti, Chiara Mele. Padova: Caterina Mian,

 http://erc.endocrinology-journals.org     © 2018 Society for Endocrinology
 https://doi.org/10.1530/ERC-17-0453          Published by Bioscientifica Ltd.
                                                     Printed in Great Britain
                                                                                                                 Downloaded from Bioscientifica.com at 03/07/2020 03:07:13PM
                                                                                                                                                               via free access
Endocrine-Related                        L Lamartina, G Grani et al.             TNM staging of DTC                                 25:3                 L11
 Cancer

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                                                                                  Received in final form 24 November 2017
                                                                                  Accepted 29 November 2017
                                                                                  Accepted Preprint published online 30 November 2017

 http://erc.endocrinology-journals.org      © 2018 Society for Endocrinology
 https://doi.org/10.1530/ERC-17-0453           Published by Bioscientifica Ltd.
                                                      Printed in Great Britain
                                                                                                                 Downloaded from Bioscientifica.com at 03/07/2020 03:07:13PM
                                                                                                                                                               via free access
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